Glanzmann's thrombasthenia is an inherited bleeding disorder caused by a defective platelet. The functional defect in this disorder is the inability of these platelets to aggregate, a process essential to hemostasis. The proposed research will unravel the molecular characteristics of this disorder which will provide a basis for the control of bleeding in this genetic disorder and lead to an understanding of the molecular basis of platelet function. There are three immediate objectives of this proposal: (1) To establish the primary lesion causing the molecular defects present in this disease. We have established that thrombasthenia platelets lack two different membrane glycoproteins. Experiments are described which will determine the cause of this pleiotropic expression, (2) To determine the relationship of the defect to bleeding in this disorder. The proposed study will indicate which of the missing membrane glycoproteins is involved in normal platelet aggregation, and (3) To develop a method suitable for genetic screening. Preliminary experiments from this laboratory suggest that carriers of this disorder have intermediate amounts of the two missing glycoproteins. In this proposal, experiments are designed to develop a method which reliably and simply quantitates the amount of glycoproteins IIb and III in a given platelet sample. This method will be used to establish a protocol for molecular diagnosis and screening of thrombasthenia.